DESCRIPTION (Applicant's Description) The aim of this work is to carry out a Pilot Study of a new form of topical photodynamic therapy (PDT) for cutaneous T cell lymphoma (CTCL). The therapy involves administration of a porphyrin precursor molecule, aminolevulenic acid (ALA), which is converted within the target cells to protoporphyrin IX (PpIX), which is a potent photosensitizer. The applicants have found that a single PDT treatment with topical ALA gives long term remissions of patch and plaque stage CTCL under conditions which cause transient epidermal necrosis. While the response is very encouraging, the epidermal necrosis makes the single treatment approach impractical for treating wide-spread disease. This pilot study will examine the feasibility a fractionated, multi-dose therapy that eliminates the malignant T cell infiltrate, but minimizes damage to the overlying epidermis. The specific goals are: To evaluate multi-treatment PDT with topical ALA in patch and thin plaque stage CTCL. a) Using different concentrations of ALA and varying times of application, to examine kinetics of, and variation in PpIX accumulation in lesions and normal skin, by non-invasive, epicutaneous, in situ measurements of PpIX fluorescence with a fiber-optic coupled, dual wavelength fluorometer; b) The microscopic distribution of PpIX within the skin and the malignant infiltrates will be determined after different application times, using intensified video digital fluorescence microscopy on frozen sections of lesional biopsies. PpIX levels will be quantitated by extraction and fluorimetric and/or HPLC techniques; c) Test if quantitative in situ PpIX fluorescence predicts a photodynamic dose range that spares the epidermis, and d) Examine whether a therapeutic regime using multiple treatments just below the maximal photodynamic damage dose (MPDD) for the epidermis is still effective against the malignant infiltrates. If so, from analysis of biopsies taken at various times during the treatment and resolution process, begin to examine the mechanisms of action. The long term goals are to use the information from this Pilot Study to guide development of a subsequent Phase I/II trial leading to a selective therapy for CTCL that will be practical to treating large areas of the body, that may be extended to use of systemic ALA therapy for thick plaque and tumor stage disease. The approach also may be feasible for Kaposi's sarcoma, recurrent breast cancer and other cutaneous lesions.